Biomedical subjects

A Leff

Publications and source records attributed to A Leff.

7 recordsLinked to original sources

PubMed1992

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

Adrenalectomy↗

PubMed1979

Tuberculosis. A chemotherapeutic triumph but a persistent socioeconomic problem.

There is evidence that man has suffered from tuberculosis for more than 5,000 years, and through crowded living conditions, debilitation, and malnutrition, tuberculosis became epidemic in Western civilization and was a major cause of mortality. Identification of the tubercle bacillus as the causative agent in 1882 firmly established the infectious nature of the disease and the development of sanatoriums soon followed. Before the advent of effective chemotherapeutic agents, treatment involved rest, diet, and various surgical procedures, which were of little or no benefit to the patient. The discovery of dihydrostreptomycin, aminosalicylic acid, and isoniazid in the late 1940s and early 1950s meant that tuberculosis was now entirely curable in virtually all patients. Despite these effective chemotherapeutic and preventive agents, tuberculosis has receded to socioeconomically disadvantaged urban and rural areas, where the incidence parallels that of developing countries. Conquest of the disease will require improved health care delivery to the indigent and dispossessed.

Antitubercular Agents↗

PubMed1979

Tuberculosis chemoprophylaxis practices in metropolitan clinics.

A survey of tuberculosis chemoprophylaxis policies was conducted from September 1977 through January 1978 of all metropolitan programs in the United States that reported more than 100 cases of tuberculosis during 1976. Twenty-eight programs were surveyed, and all responded. Uniform practice was found with regard to the dosage of isoniazid administered, duration of treatment, and most other indications for preventive therapy recommended by the American Thoracic Society and the U.S. Public Health Service Center for Disease Control. One third of the programs surveyed administered chemoprophylaxis to pregnant women, and one third regularly dispensed more than a one-month supply of isoniazid to patients. Three programs (11%) routinely monitored hepatic function by serum laboratory tests during chemoprophylaxis. Four programs (14%) regularly or occasionally used bacillus Calmette-Guérin vaccine for prevention of tuberculosis. Although large metropolitan programs generally followed the guidelines of the American Thoracic Society and the Center for Disease Control for tuberculosis chemoprophylaxis, some major variances in practice were reported.

Adult↗

PubMed1979

The pathogenesis of pulmonary and miliary tuberculosis.

Tuberculosis is spread from human to human by airborne transmission; it is not a highly infectious disease. Primary infection remits in 90% of cases and is progressive in the remainder; it is accompanied by lymphohematogenous seeding of many organs, and reactivation may occur as early as three months or many years after initial infection. Primary infection generally confers immunity from subsequent reinfection. The risk of reactivation of tuberculosis is greatest in the year after infection, declining sharply thereafter for most patients. Acute miliary tuberculosis has a distinctive pathogenesis that is different from localized postprimary disease. Miliary tuberculosis may appear in a patient with a normal chest roentgenogram; even in patients with abnormal chest roentgenograms, sputum cultures for acid-fast organisms may be negative. Transbronchial biopsy is the preferred method of diagnosis and prompt initiation of treatment is essential.

Adult↗

PubMed1979

Public health and preventive aspects of pulmonary tuberculosis. Infectiousness, epidemiology, risk factors, classification, and preventive therapy.

Tuberculosis is usually of a low order of infectivity. Once treatment has begun, patients are no longer infectious to close contacts, and there is no benefit to isolating them. Among the risk factors associated with tuberculosis that reactivates after many years of dormant infection, the coexistence of silicosis, diabetes mellitus, and the postgastrectomy state with tuberculosis are reasonably well demonstrated. Preventive treatment begins with prompt institution of chemotherapy in the index case. Isoniazid is extremely effective in preventing tuberculosis infection from becoming tuberculosis disease. The benefits of BCG vaccine are controversial, and it is little used in the United States. Hepatotoxicity is a potential serious side effect of isoniazid chemoprophylaxis. Clinical monitoring for prodromal symptoms makes the drug safe and effective for patients under 35 years of age.

Adult↗

PubMed1978

Pleural effusion from malignancy.

Pleural effusion from metastatic malignancy can cause major impairment of respiratory function and eventual death. Although cure is not possible, successful palliative treatment allows months to years of productive life, obviating the need for continuous hospitalization and repeated thoracenteses. Successful palliative treatment requires obliteration of the pleural space. Literature survey indicates that a wide variety of medical agents and surgical methods have been used with variable success. Medical methods include instillation of antineoplastic agents, antimicrobial agents, or colloidal radioisotopes into the pleural space; quinacrine and tetracycline are moderately to highly effective agents, but the toxicity of the former is substantial. Bedside talc poudrage with thoracostomy-tube drainage is a safe and highly effective alternative. Pleurectomy is the definitive method of preventing reaccumulation of pleural fluid that results from metastatic malignancy, even when other methods have failed, but thehigh morbidity and mortality of the procedures mandate careful patient selection.

Anti-Bacterial Agents↗

PubMed1977

Bacillus cereus pneumonia. Survival in a patient with cavitary disease treated with gentamicin.

Cavitary pneumonitis due to Bacillus cereus occurred in a patient with acute lymphoblastic leukemia. Pneumonia due to this organism is uncommon and recovery has not been previously reported. The present report is the first description of cavitary pneumonia due to B. cereus with a successful outcome. Recovery was attributed to appropriate antimicrobial therapy and induction of leukemic remission with chemotherapy.

Adult↗